The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

ObjectiveMetabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS.MethodsEighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) ≥15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters.ResultsFifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS?OSA). Compared with MS?OSA patients, MS+OSA patients had higher levels of IMT (661 ± 117 vs. 767 ± 140 μm), PWV (9.6 ± 1.0 vs. 10.6 ± 1.6 m/s), and CD (6705 ± 744 vs. 7811 ± 862 μm) (P < 0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R² = 0.42); AHI and systolic blood pressure (R² = 0.38); and AHI, age, abdominal circumference and systolic blood pressure (R² = 0.45), respectively. The R² of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively.ConclusionsOSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS.     

Mandibular advancement splint titration in obstructive sleep apnoea

Introduction  Mandibular advancement splints (MAS) allowing self-adjustment may be better tolerated, but the optimum titration protocol needs systematic study. Aim  The aims of the study are to assess the effectiveness of a titratable MAS device in consecutive patients with body mass index (BMI) < 35 kg/m² and obstructive sleep apnoea [OSA, apnoea–hypopnoea index (AHI) 10–40/h] and compare two methods of adjustment [self-adjustment or adjustment after polysomnographic (PSG) feedback]. Materials and methods  Twenty-eight patients (24 M, mean age 49 years, mean BMI 27.6 kg/m²) with symptomatic (Epworth Sleepiness score > 8/24, snoring, choking or poor sleep quality) OSA (mean AHI 25.7/h, range 10–46/h) had a MAS set at 70% maximal protrusion and were randomised to subjective self-adjustment for 6 weeks (n = 16) or objective adjustment (n = 12; fixed position for 3 weeks, then PSG based feedback at 3 weeks with self-adjustment instructions). Primary outcome variable (AHI) and OSA symptoms were compared by t tests and chi-squared tests at baseline and after 6 weeks. Resolution of apnoea was defined as AHI < 5/h; improvement was defined as AHI decreased by >50% but still >5/h. Results  The groups had similar baseline demographics, OSA severity and occlusal type. MAS therapy improved or resolved OSA in 20 out of 28 (71%) and was reportedly used nightly by 91% of the objective group and 63% of the subjective group (p = 0.04). MAS were used all night by 75% of the objective group and 69% of the subjective group (p > 0.05). MAS adjustment following PSG feedback did not lower AHI further from 3 weeks (baseline 26.5 ± 12.0/h, 3 weeks 15.3 ± 13.5/h p = 0.01, 6 weeks 11.7 ± 10.0/h, p = 0.11). The overall improvement was similar to that achieved with subjective adjustment (baseline AHI 25.4 ± 7.4/h, 6 weeks 14.3 ± 10.7/h, p = 0.0002). Symptomatic benefit was reported by both groups. Conclusion  In selected patients, titratable MAS improved or resolved OSA in the majority of patients and was well tolerated. PSG-based feedback at 3 weeks allowed objective confirmation of efficacy and increased device use but did not result in greater improvement in AHI or symptoms. Neither titration method was significantly superior for us to provide firm endorsement. However, we recommend a follow-up sleep study to confirm MAS efficacy.     

Intima-Media Thickness in Patients With Obstructive Sleep Apnea Without Comorbidities

Background

Obstructive sleep apnea (OSA) is associated with elevated risk of cardiovascular events. The early stages of vascular complications can be visualized by means of ultrasound. Intima-media thickness (IMT) correlates with the presence of risk factors of cardiovascular diseases such as hypertension, diabetes, tobacco smoking, or hyperlipidemia. However, little is known whether OSA itself may be the cause of IMT thickening.

Methods

The study group was composed of 28 patients (6 women, 22 men; mean age = 53.8 years, mean BMI = 27.1 kg/m², mean AHI = 22.4/h) with OSA who had no comorbidities. The control group consisted of 28 healthy subjects (6 women, 22 men; mean age = 53.9 years; mean BMI = 27.5 kg/m²). In both groups IMT was assessed in common carotid arteries with the use of ultrasonography. Additionally, in patients with OSA, pulse wave velocity, echocardiography, 24-h automated blood pressure monitoring, clinical signs and symptoms, and blood tests were performed to investigate possible correlations with IMT.

Results

Median IMT was 0.41 mm in OSA patients and 0.46 mm in the control group (p = 0.087). Echocardiography revealed left ventricle hypertrophy in 21 %, systolic disorders in 8 %, and diastolic disorders in 57 % of the patients. In a large majority of patients, pulse wave velocity was found to be normal. IMT correlated with age (r = 0.446, p = 0.017), total cholesterol (r = 0.518, p = 0.005), daytime systolic blood pressure (r = 0.422, p = 0.025), pulse pressure 24 h and daytime (r = 0.424, p = 0.027 and r = 0.449, p = 0.019), early mitral flow/atrial mitral flow (E/A) (r = ?0.429, p = 0.023), and posterior wall diameter (PWD) (r = 0.417, p = 0.270).

Conclusion

In a relatively nonobese group of patients, no significant differences were found in the intima-media thickness between OSA patients without concomitant cardiovascular diseases and healthy controls. This may lead to the conclusion that IMT does not reflect increased risk of cardiovascular events in patients with isolated OSA.     

Vascular alterations in apolipoprotein A-I amyloidosis (Leu75Pro). A case–control study

Background: Among hereditary amyloidoses, apolipoprotein A-I (APO A-I) amyloidosis (Leu75Pro) is a rare, autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated.

Objective: To investigate vascular structural as well as functional alterations.

Methods: In 131 carriers of the amyloidogenic Leu75Pro APO A-I mutation (mean age 52?+?16 years, 56 women) and in 131 subjects matched for age, sex, body mass index and clinic blood pressure (BP), arterial stiffness (pulse wave velocity, PWV) and carotid intima-media thickness (IMT) were measured.

Results: By definition no differences for age, sex, body mass index, and BP were observed. Meanmax IMT (Mmax–IMT) in the common (CC), bifurcation (BIF) and internal (ICA) carotid artery were comparable in the two groups. After adjustment for high-density lipoprotein cholesterol and renal function differences between the two groups, a lower meanmax–IMT was observed in APO A-I Leu75Pro mutation carriers than in controls (CC Mmax–IMT 0.87?±?0.21 versus 0.93?±?0.2?mm, p?=?0.07; BIF Mmax–IMT 1.19?±?0.48 versus 1.36?±?0.46?mm, p?=?0.025; ICA Mmax–IMT 0.9?±?0.37 versus 1.02?±?0.35?mm, p?=?0.028). On the other hand, aortic stiffness was significantly greater in patients with APO A-I amyloidosis than controls (PWV 11.5?±?2.9 and 10.7?±?2.3?m/s, p?<?0.05), even after adjusting for confounders.

Conclusions: In carriers of the amyloidogenic Leu75Pro APO A-I mutation, a significant increase in arterial stiffness is observed; on the contrary, carotid artery IMT is comparable to that of control subjects. These results may add significant information to the clinical features of this rare genetic disorder.     

Descriptive study of the relationship between the subclinical carotid disease and biomarkers,carotid femoral pulse wave velocity in patients with hypertension

Background: Carotid intima-media thickness (cIMT) is a significant early prediction signal for preclinical atherosclerosis. Plasma homocysteine (Hcy) level is an independent risk factor for cardiovascular diseases. Pulse wave velocity (PWV), an index of arterial stiffness (AS), has showed its value in the evaluation of AS in vascular-related diseases. The data regarding the relationships between cIMT and other indices of vascular damage are limited and partly controversial. We aim to investigate the relationships between cIMT and other indices of vascular damage such as Hcy and carotid femoral PWV (CF-PWV). Methods: In total,1188 (male/female 514/674) subjects with hypertension from Vascular Medicine of Peking University Shougang Hospital were enrolled into our study. The patients with hypertension were measured bilateral cIMT by B-mode ultrasound and measured plasma levels of Hcy, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein (CRP), glucose, and other biomarkers. Plaques were detected in 78% of the study patients. Plasma Hcy (p < 0.001), CRP (p <  0.001), LDL (p < 0.001), HDL (p = 0.008), TC levels (p < 0.001), and CF-PWP (p < 0.001) were significantly greater in hypertensive patients with carotid plaques than patients without. The carotid plaque detection rate (p < 0.001) and bilvertebral artery max velocity (p < 0.05) were significantly different in quartiles of plasma Hcy levels. R-IMT correlated significantly with HCY, high sensitive CRP (hs-CRP), CF-PWV, and R-vertebral artery intimal diameter. Age (p < 0.001) and CF-PWV (p < 0.05) predicted the presence of carotid plaques independently in the logistic regression. However, Hcy did not independently predict the presence of carotid plaques in the logistic regression. Conclusion: Increased carotid femoral PWV and elevated plasma Hcy levels are associated with subclinical carotid disease in hypertensive patients. CF-PWV independently predicted subclinical carotid plaque in the patients with hypertensive. While, there is insufficient evidence for Hcy in predicting plaque incidence.     

Determinants of carotid artery wall thickening in young patients with Type 1 diabetes mellitus

To investigate associations between early atherosclerosis and possible risk factors for it in young patients with established Type 1 diabetes mellitus (DM), we measured the combined intima-media thickness (IMT) of the common carotid arteries with high resolution ultrasound in 310 young patients (age ≤ 40 years, mean 27.9 ± 6.5) with a diabetes duration ≥ 2 years, and in two control groups of similar age (control 1:40 healthy subjects, control 2: 40 Type 1 DM recently diagnosed patients). Albumin excretion rate and lipids (total cholesterol and triglycerides) were measured and retinopathy and hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg) sought in the patients. Mean maximum IMT was 0.52 ± 0.06 mm in control group 1 and 0.50 ± 0.05 mm in control group 2 with a mean difference of 0.02 mm (95% CI: −0.01, 0.04). The more established Type 1 DM patients had a significantly greater IMT (0.57 ± 0.13 mm, p < 0.001) than both control groups. In a subgroup analysis, patients with microvascular diabetic complications (n = 99) had a significantly greater IMT (0.63 ± 0.17 vs 0.55 ± 0.10 mm, p < 0.001) than those without (n = 211). In a multiple linear regression analysis with a significance level of ≤ 0.10, the carotid artery IMT of our established diabetic patients was related to age, male gender, triglycerides and nephropathy, suggesting the latter as the main diabetes-specific risk for intima-media thickening in young Type 1 DM patients. © 1998 John Wiley & Sons, Ltd.     

Arterial properties in acromegaly: relation to disease activity and associated cardiovascular risk factors

Purpose

Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function.

Methods

Twenty-nine subjects with acromegaly (11 males, 52 ± 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD).

Results

IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 ± 1.1 in patients with active disease versus 0.7 ± 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 ± 2.7 % in active acromegaly, 4.4 ± 3.3 % in controlled acromegaly and 7.5 ± 3.8 % in controls; p = 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r = 0.4; P = 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46; p = 0.017) and negatively with small vessel compliance (r = ?0.44, p = 0.02).

Conclusions

Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.

     

The effects of continuous positive airway pressure therapy on mean platelet volume in patients with obstructive sleep apnea

Previous studies have reported increased platelet activation and aggregation in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) treatment has been shown to decrease platelet activation. We aimed to study the effects of nasal CPAP therapy has on MPV values in patients with severe OSA. Thirty-one patients (21 men; mean age 53.8?±?9.2 years) with severe OSA (AHI?>?30 events/hour) constituted the study group. An age, gender and body mass index (BMI) matched control group was composed 25 subjects (14 men; mean age 49.6?±?8.5 years) without OSA (AHI?<?5 events/hour). We measured MPV values in patients with severe OSA and control subjects and we measured MPV values after 6 months of CPAP therapy in severe OS patients. The median (IQR) MPV values were significantly higher in patients with severe OSA than in control group (8.5 [8.3–9.1] vs. 8.3 [7.5–8.8] fL; p?=?0.03). The platelet counts were significantly lower in patients with severe OSA than in control group (217.8?±?45.9 vs. 265.4?±?64.0?×?10⁹/L; p?=?0.002). The six months of CPAP therapy caused significant reductions in median (IQR) MPV values in patients with severe OSA (8.5 [8.3–9.1] to 7.9 [7.4–8.2] fL; p?<?0.001). Six months of CPAP therapy caused significant increase in platelet counts when compared with baseline values (217.8?±?45.9 to 233.7?±?60.6?×?10⁹/L; p?<?0.001). We have found that the MPV values of patients with severe OSA were significantly higher than those of the control subjects and 6 months CPAP therapy caused significant reductions in the MPV values in patients with severe OSA.     

Parameters of arterial function and structure in adult patients after coarctation repair

Regardless of a successful operation, patients with coarctation of aorta (CoAo) are exposed to the risk of hypertension and a propensity to vascular and end-organ damage. The aim of this study is to evaluate the influence of residual aorta stenosis as well as the age at the operation on the parameters of arterial function and structure in patients after CoAo repair. Eighty-five patients after CoAo repair (53 males; mean age: 34.6 ± 10.3 years, mean age at the repair: 10.9 ± 8.2 years) were enrolled in the study. The control group consisted of 30 healthy subjects (18 males; mean age: 33.6 ± 8.2 years). Indices of systemic arterial remodeling [flow-mediated dilatation (FMD), nitroglycerine-mediated vasodilatation (NMD), carotid intima-media thickness (IMT), pulse wave velocity (PWV)] were analyzed in all study patients. In normotensive patients after CoAo repair (47/55%), a significantly increased PWV was observed in comparison to the control group (6.8 ± 1.2 vs. 5.4 ± 0.9 m/s; p = 0.003), with no difference in IMT values (0.53 ± 0.1 vs. 0.51 ± 0.1 mm; p = 0.06). Mean FMD (4.8 ± 2.8 vs. 8.5 ± 2.3%; p = 0.00003) and NMD (11.3 ± 4.6 vs. 19.8 ± 7.2%; p = 0.00001) were lower than in the controls. In patients with a residual aorta stenosis (46/54%), defined as an arm-leg pressure gradient ≥20 mmHg, no differences were found within the scope of both systolic and diastolic blood pressure and of all of the examined vascular parameters. No significant correlations were revealed between the vascular parameters and the gradient across descending aorta as well as the age at the operation. Residual stenosis in the descending aorta does not affect the arterial vasodilatation nor stiffness in patients after CoAo repair. An early surgery does not influence the remodeling of the vessels, which supports the thesis that CoAo is a generalized vascular disease and that even an early operation cannot prevent the progressive and vascular changes and end-organ damage.     

Reverse atrial electrical remodelling induced by continuous positive airway pressure in patients with severe obstructive sleep apnoea

Background

Obstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and mortality, including atrial arrhythmias. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; its impact on atrial electrical remodelling has not been fully investigated. Signal-averaged p-wave (SAPW) duration is an accepted marker for atrial electrical remodelling.

Objective

The objective of this study is to determine whether CPAP induces reverse atrial electrical remodelling in patients with severe OSA.

Methods

Consecutive patients attending the Sleep Disorder Clinic at Kingston General Hospital underwent full polysomnography. OSA-negative controls and severe OSA were defined as apnoea–hypopnea index (AHI)?<?5 events/hour and AHI?≥?30 events/hour, respectively. SAPW duration was determined at baseline and after 4–6 weeks of CPAP in severe OSA patients or without intervention controls.

Results

Nineteen severe OSA patients and 10 controls were included in the analysis. Mean AHI and minimum oxygen saturation were 41.4?±?10.1 events/hour and 80.5?±?6.5 % in severe OSA patients and 2.8?±?1.2 events/hour and 91.4?±?2.1 % in controls. At baseline, severe OSA patients had a greater SAPW duration than controls (131.9?±?10.4 vs 122.8?±?10.5 ms; p?=?0.02). After CPAP, there was a significant reduction of SAPW duration in severe OSA patients (131.9?±?10.4 to 126.2?±?8.8 ms; p?<?0.001), while SAPW duration did not change after 4–6 weeks in controls.

Conclusion

CPAP induced reverse atrial electrical remodelling in patients with severe OSA as represented by a significant reduction in SAPW duration.     

Gender differences in clinical and polysomnographic features of obstructive sleep apnea: a clinical study of 2827 patients

Purpose

Obstructive sleep apnea (OSA) is underdiagnosed in females due to different clinical presentation. We aimed to determine the effect of gender on clinical and polysomnographic features and identify predictors of OSA in women.

Methods

Differences in demographic, clinical, and polysomnographic parameters between 2052 male and 775 female OSA patients were compared.

Results

In female OSA patients, age (56.1 ± 9.7 vs. 50.4 ± 11.6 years, p < 0.0001) and body mass index (36.3 ± 8.6 vs. 31.8 ± 5.9 kg/m², p < 0.0001) were increased, whereas men had higher waist-to-hip ratio and neck circumference (p < 0.0001). Hypertension, diabetes mellitus, thyroid disease, and asthma were more common in females (p < 0.0001). Men reported more witnessed apnea (p < 0.0001), but nocturnal choking, morning headache, fatigue, insomnia symptoms, impaired memory, mood disturbance, reflux, nocturia, and enuresis were more frequent in women (p < 0.0001).

The indicators of OSA severity including apnea-hypopnea index (AHI) (p < 0.0001) and oxygen desaturation index (p = 0.007) were lower in women. REM AHI (p < 0.0001) was higher, and supine AHI (p < 0.0001) was lower in females. Besides, women had decreased total sleep time (p = 0.028) and sleep efficiency (p = 0.003) and increased sleep latency (p < 0.0001). In multivariate logistic regression analysis, increased REM AHI, N3 sleep, obesity, age, morning headache, and lower supine AHI were independently associated with female gender.

Conclusions

These data suggest that frequency and severity of sleep apnea is lower in female OSA patients, and they are presenting with female-specific symptoms and increased medical comorbidities. Therefore, female-specific questionnaires should be developed and used for preventing underdiagnosis of OSA.

     

Performance of questionnaires aimed at detecting sleep disorders in patients attending a hypertension center

Introduction: Hypertension (HT) and obstructive sleep apnea-hypopnea syndrome (OSA) are prevalent and frequently related pathologies. The predictive value of screening questionnaires in cardiovascular settings is not totally clear and could be useful to select candidates for the sleep test.

Materials and Methods: We performed a prospective study in adults with suspected HT referred to a day-care hospital. Epworth Sleepiness Scale (ESS), Berlin, and STOP-BANG (SBQ) questionnaire were checked against data from home-based respiratory polygraphy (RP). We calculated sensitivity (S) and specificity (Sp), positive and negative predictive values (PPV and NPV), and the area under the ROC curve (AUC-ROC) for each questionnaire and their combinations.

Results: We analyzed 382 patients; 234 men (61.3%) and 148 women, mean age: 54.5 ± 13.7 years, body mass index (BMI): 33.1 ± 7.8 kg/m², ESS: 7.4 ± 4.7. Seventy-eight percent had an apnea-hypopnea index (AHI) >5 events per hour (eV/h) and 58% presented >15 eV/h (mean: 17.5 ± 9.3 eV/h). With regard to clinically significant OSA (AHI > 15 eV/h), 5 SBQ components showed S: 100% (CI: 97–100) and Sp: 98% (CI: 95–99) with a NPV of 100, a PPV of 97.8, and an AUC-ROC of 0.90 (p < 0.0001). ESS > 10 + high-risk Berlin did not perform as effectively.

Conclusion: In a population of HT patients, SBQ > 5 performed better at identifying patients with >15 eV/hour with a high discrimination power.     

Metabolic syndrome is related to vascular structural alterations but not to functional ones both in hypertensives and healthy subjects

Background and aimsMetabolic Syndrome (MS) has been related to an impairment in arterial structural and functional properties with heterogeneous results. In this paper we focused on the effects of MS on arterial carotid-femoral PWV and common carotid IMT in two different populations, one of hypertensive patients and one of healthy controls.Methods and resultsWe enrolled 816 consecutive HT and 536 healthy controls. Vascular structural (IMT) and functional (PWV) properties were evaluated. NCEP-ATP-III criteria were used for diagnosis of MS. MS was diagnosed in 26.9% and 6.9% in hypertensive and control subjects, respectively. PWV was similar in controls with and without MS (7.7 ± 1.9 vs 7.6 ± 1.1 m/s, p = 0.69), while IMT was higher in controls with than those without MS (0.64 ± 0.18 vs 0.57 ± 0.13 mm, p = 0.02). Hypertensives with MS were older (57.9 ± 12.2 vs 52.7 ± 14.1 years, p < 0.001) and showed higher PWV (9.0 ± 2.3 vs 8.4 ± 2.1 m/s, p = 0.001) and IMT (0.72 ± 0.22 vs 0.65 ± 0.17 mm, p < 0.001) than those without MS, however at the age-adjusted analysis only the difference in IMT was confirmed (p = 0.007). Regression models showed that MS was an independent determinant of IMT in both controls (β = 0.08, p = 0.03) and hypertensives (β = 0.08, p = 0.01), but not of PWV either in controls (β = 0.006, p = 0.886 and β = 0.04, p = 0.19, respectively).Conclusionsthe main finding of our work is that MS is a significant determinant of IMT while this is not the case for PWV. This result have been confirmed both in hypertensive subjects and in healthy controls.     

The association of early atherosclerosis and retinopathy in adolescents with type 1 diabetes: preliminary report

Recent studies have shown a close correlation between advanced diabetic retinopathy and the late stages of atherosclerosis. The purpose of this study was to analyse the association between diabetic retinopathy and early atherosclerotic changes in adolescents with type 1 diabetes. We studied 28 adolescents with type 1 diabetes. Eight patients with nonproliferative retinopathy were compared with the remaining 20 patients, and with 11 healthy controls. The function of endothelium was assessed by measuring flow-mediated dilatation (FMD), the intima-media thickness (IMT) of the common carotid arteries and adhesion molecules (sICAM-1, sVCAM-1, sE-selectin). In the group with retinopathy FMD equalled 7.8±4.1% vs. 12.1±5.1% in the control group (p=0.04), and in the group without retinopathy, 7.6±5.5% (p=0.04 compared to controls). Higher IMT was found in all patients with diabetes in comparison with healthy controls: 0.49±0.06 mm vs. 0.42±0.03 mm (p=0.001). Patients with retinopathy had a significantly higher value of IMT in comparison not only with controls but also with patients without complications: 0.56±0.06 mm vs. 0.47±0.03 mm (p=0.0001). Adhesion molecule levels were not changed in patients with retinopathy. Higher IMT was found in adolescents with diabetic retinopathy in comparison with patients without complications, which may suggest that macrovascular changes are more advanced in these patients than in their diabetic peers without retinopathy.     

Obstructive sleep apnea is associated with interdialytic weight gain and increased long-term cardiovascular events in hemodialysis patients

Background

Obstructive sleep apnea (OSA) is common in hemodialysis (HD) patients. The reasons for the high prevalence and whether OSA is associated with vascular impairment, end-organ damage, and prognosis are not completely clear.

Methods

We evaluated patients with low cardiovascular risk on HD, not treated by CPAP. Laboratory tests, sleep questionnaires (Berlin and Epworth) and polysonography studies, echocardiography, and markers of arterial stiffness and atherosclerosis were performed. After the initial evaluation, patients were followed up until cardiovascular events, renal transplantation, or death.

Results

Fifty-five patients (49% male, 50?±?9 years, body mass index 24.7?±?4.5 kg/m²) were included. OSA (apnea-hypopnea index ≥?5 events/h) occurred in 73% of the patients. The proportion of patients with interdialytic weight gain >?2 kg was higher in patients with OSA than those without OSA (96 vs. 55%; p?=?0.002). Left ventricular (LV) posterior wall thickness (10.0?±?1.9 vs. 11.3?±?1.8 mm; p?=?0.04) and LV diastolic diameter (48?±?5 vs. 53?±?5 mm; p?=?0.003) were higher in patients with OSA than in patients without OSA, respectively. Sleep questionnaires did not predict OSA. No significant differences were found in pulse wave velocity, carotid intima-media thickness, and ankle-brachial index between the groups. Multivariate analysis showed that interdialytic weight gain >?2 kg and LV diastolic diameter were independently associated with OSA. On follow-up (median 45 months), OSA was found to be associated with a higher incidence of cardiovascular (CV) events (28 vs. 7%, log-rank?=?0.042).

Conclusions

OSA was associated with increased risk of CV events. Significant (>?2 kg) interdialytic weight gain was independently associated with OSA.

     

Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up

Cilostazol, a phosphodiesterase III inhibitor, is known to have anti-proliferative activity. We investigated the effects of cilostazol 200 mg, in addition to aspirin 100 mg and clopidogrel 75 mg, on carotid intima-media thickness (IMT) progression during a 2-year follow-up period in patients with acute coronary syndrome (ACS) requiring stent implantation. Patients with ACS (n = 130) were randomly assigned to the cilostazol group (n = 64) or the control group (n = 66). Longitudinal images of left and right carotid IMT were measured at baseline, at 6, 12, and 24 months using a 10-MHz linear vascular probe. The primary endpoint was to compare the changes in maximum carotid IMT at 2 years. Other parameters such as inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and adiponectin] and bleeding risk were also compared. The carotid IMT showed no significant progression from baseline in the cilostazol group compared to significant progression in the control group at 12 months (0.78 ± 0.38 and 0.85 ± 0.41 mm, p = 0.034, respectively) and 24 months (0.82 ± 0.41 and 0.96 ± 0.39 mm, p = 0.022, respectively). Major bleeding (p = 1.00), minor bleeding (p = 0.68), and total bleeding rates (p = 0.74) were similar between the two groups during the 2-year follow-up. Decreases from baseline in IL-6 (−2.79 ± 2.83 and −2.14 ± 3.36 pg/ml, p = 0.010, respectively) and TNF-α (−2.81 ± 1.97 and −2.21 ± 2.68 pg/ml, p = 0.029, respectively) were significantly greater in the cilostazol group than the control group during the follow-up. Cilostazol treatment, with greater anti-inflammatory effect, inhibited the progression of carotid IMT without increasing the risk of bleeding in patients with ACS during the 2-year follow-up.     

Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists

Objectives

Obesity is the main risk factor for the development of obstructive sleep apnea (OSA). Hyperprolactinemia has also been related to obesity. To determine the OSA prevalence in patients with prolactinoma before and after dopamine agonist (DA) and to evaluate the correlation between the apnea-hypopnea index (AHI) and prolactin levels, body mass index (BMI), waist circumference (WC), visceral fat volume (VFV), subcutaneous fat volume, and other metabolic parameters.

Methods

Thirty-five patients with prolactinoma at baseline and twenty-one who completed the 6-month DA treatment were submitted to clinical/laboratorial evaluations, polysomnography and abdominal imaging.

Results

Before treatment, the prevalence of obesity/overweight and OSA were, respectively, 68.5 and 34.2 %. We found a positive correlation between AHI and weight (r = 0.57; p < 0.001), BMI (r = 0.56; p < 0.001), WC (r = 0.61; p < 0.001), VFV (r = 0.55; p = 0.002), insulin levels (r = 0.57; p < 0.001), and HOMA-IR index (r = 0.57; p < 0.001); and a negative correlation between AHI and HDL-cholesterol (r = ?0.47; p = 0.005). After multivariate analysis, VFV and insulin levels were the most important predictors for AHI (p = 0.001 and p = 0.02, respectively). After DA, the obesity/overweight and OSA prevalence did not change.

Conclusions

The OSA prevalence in patients with prolactinoma is similar to the obese subjects and did not change after treatment. Higher BMI and visceral obesity, but not prolactin levels, seem to be the major factor involved in the occurrence of OSA in these patients.     

Influence of obstructive sleep apnea on left ventricular mass and global function: sleep apnea and myocardial performance index

Obstructive sleep apnea (OSA) is associated with cardiovascular mortality and morbidity. It may predispose patients to left ventricular hypertrophy and heart failure. The aim of this study was to determine the left ventricular mass (LVM) and myocardial performance index (MPI) reflecting left ventricular global function in uncomplicated OSA patients. Sixty-four subjects without hypertension, diabetes mellitus, and any cardiac or pulmonary disease referred for evaluation of OSA underwent overnight polysomnography and complete echocardiographic assessment. According to the apnea hypopnea index (AHI), subjects were divided into three groups: group 1, control subjects with nonapneic snorers (AHI < 5, n = 18); group 2, patients with mild to moderate OSA (AHI: 5–30, n = 25); and group 3, severe OSA (AHI > 30, n = 21). Basic echocardiographic measurements, LVM, and LVM index were measured. Left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by Doppler echocardiography. There were no significant differences in age, sex, body mass index, heart rate, and systolic and diastolic blood pressure among the three groups. Left atrium, interventricular septum, left ventricular posterior wall, left ventricular end-diastolic and end-systolic diameters, LVM mass, and LVM index were not significantly different among the three groups. Left ventricular MPI was significantly higher in severe OSA patients (0.64 ± 0.18) than in controls (0.49 ± 0.18; P < 0.05). There was no significant difference between controls (0.49 ± 0.18) and mild to moderate OSA (0.61 ± 0.16; P = 0.08) and between mild to moderate OSA (0.61 ± 0.16) and severe OSA (0.64 ± 0.18; P = 0.84). The present study demonstrates that patients with severe OSA have global left ventricular dysfunction.     

No correlation and low agreement of imaging and inflammatory atherosclerosis' markers in familial hypercholesterolemia

Our purpose was to study the determinants of coronary and carotid subclinical atherosclerosis, aortic stiffness and their relation with inflammatory biomarkers in familial hypercholesterolemia (FH) subjects. Furthermore, we evaluated the agreement degree of imaging and inflammatory markers’ severity used for coronary heart disease (CHD) prediction. Coronary calcium scores (CCS), carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV), C reactive protein (CRP) and white blood cells count (WBC) were determined in 89 FH patients (39 ± 14 years, mean LDL-C = 279 mg/dl) and in 31 normal subjects (NL). The following values were considered as imaging and biomarkers’ severity: CCS > 75th% for age and sex, IMT > 900 μm, PWV > 12 m/s, and CRP > 3 mg/l.Coronary artery calcification (CAC) prevalence and severity, IMT, PWV and WBC values were higher in FH than in NL (all parameters, p < 0.05). After multivariate analysis, the following variables were considered independent determinants of (1) IMT: systolic blood pressure, 10-year CHD risk by Framingham risk scores (FRS) and apolipoprotein B (r² = 0.33); (2) PWV: age (r² = 0.35); (3) CAC as a continuous variable: male gender and LDL-cholesterol year score (LYS) (r² = 0.32); (4) presence of CAC as dichotomous variable: FRS (p = 0.0027) and LYS (p = 0.0228). With the exception of a moderate agreement degree between IMT and PWV severity (kappa = 0.5) all other markers had only a slight agreement level (kappa < 0.1). In conclusion, clinical parameters poorly explained IMT, CAC and PWV variability in FH subjects. Furthermore, imaging markers and inflammatory biomarkers presented a poor agreement degree of their severity for CHD prediction.     

Dietary quality and carotid intima media thickness in type 1 and type 2 diabetes: Follow-up of a randomised controlled trial

Background and aims

The relationship between dietary intake and carotid intima media thickness (IMT) and pulse wave velocity (PWV) in individuals with type 1 and type 2 diabetes has not been well studied. We investigated the association between dietary intake and common carotid artery intima media thickness (CCA IMT) and PWV in a cohort with type 1 and type 2 diabetes.